Electronic data document for use in clinical trial verification system and method

ABSTRACT

The present invention provides an electronic data document (EDD) and related system and method for use in a computerized clinical trial verification system. In an exemplary embodiment, the EDD is authenticated by the creator and validated by the receiver, and comprises an image of a source document (SD) that comprises a masked record of at least one interaction between a clinical trial investigator and a patient enrolled in a clinical trial, at least one revealed portion of the SD that includes evidence relevant to at least one question in a clinical trial questionnaire, and at least one annotation connecting the revealed portion to the at least one question. The present invention provides a computerized system and method for allowing a clinical trial investigator to answer questions from a clinical trial questionnaire pertinent to a clinical trial of a medical treatment using encrypted and partially masked electronic documents comprising images of original patient records. The process of creating and viewing the partially masked electronic documents preferably does not create local copies that can be recalled later.

This application is a Continuation of U.S. Pat. Application No.16/919,396, filed Jul. 2, 2020, entitled “Electronic Data Document ForUse in Clinical Trial Verification System and Method,” which is aContinuation of U.S. Pat. No. 10,706,958, filed Apr. 6, 2016, entitled“Electronic Data Document For Use in Clinical Trial Verification Systemand Method,” which claims priority to U.S. Provisional Pat. ApplicationNo. 62/257,974, filed Nov. 20, 2015, entitled “Clinical Trial SourceDocument Verification System and Method,” which are hereby incorporatedby reference in their entirety.

This idea pertains to the field of clinical research, in whichexperimentation is conducted upon human beings in order to assess thesafety and efficacy of new medical treatments. The time required for anew compound to go from discovery to market is approximately 12 years,with as much as half that time spent in clinical trial testing. It isestimated that only one out of every 5000 newly discovered compoundsever reach the market. It is important for pharmaceutical companies tobe able to ascertain not only which drugs will succeed, but also whichdrugs will fail the rigors of experimentation as quickly as possible. Inaddition, since the timeframe for patent protection begins when a newcompound is discovered and patent protection is sought, each day lost inthe clinical trial process may be time lost in the period when a drugcan be marketed under patent protection.

The process of data collection for a clinical trial begins with aninteraction between a physician (the Investigator) and a patient (theSubject). This interaction is documented in writing in the patient’smedical record and considered to be a legal document. The medical recordconsists primarily of alphanumeric characters written by the physicianto describe the interaction with the patient and is considered to be thefirst moment in time when a record is created: this is referred to asthe Source Document (SD). The physician records information in the SDabout the patient’s complaints, prior conditions, medications,allergies, physical examination findings, lab tests, imaging tests, andplan, for example. For purposes of clinical research, however, only asubset of the information in the SD is needed. For example, a clinicaltrial about hypertension might only require information about bloodpressure, and even though the SD might also contain information writtenby the doctor about the patient’s prostate exam, only the blood pressureneeds to be extracted as relevant data from the SD.

Manufacturers of medical treatments will frequently recruit the help ofInvestigators to conduct clinical studies. These manufacturers are knownas Sponsors. Sponsors will create forms (also known as a case reportform or CRF) that should be filled out by the Investigators and/or theirhospital staff. The CRF contains questions about the Subject relevant tothe clinical trial. Answers to these questions must be submitted by theInvestigator in order for the Sponsor to gather data about the efficacyand safety of their medical treatment. Until recently, the CRF has beena paper document, completed by the Investigator using their ownhandwriting. Upon completion of the CRF, the Investigator transmits theCRF to the Sponsor, usually by fax or by mailing copies. Upon receipt ofthe CRF, the Sponsor then transcribes information from the CRF into adatabase. Since this transcription process is a point for potentialhuman error, Sponsors will often enter the data twice and laterreconcile any errors of transcription. This process is known as doubledata entry (DDE).

It is recognized that another potential step that may lead to humanerror is the process in which information is transcribed by theInvestigator or their staff from the SD into the CRF. In order tominimize this potential for error, Sponsors perform a process in whichthe information written on the CRF is checked against the information inthe SD. This process is known as Source Document Verification (SDV). Inpractice, this requires personnel representing the Sponsor to carry theCRF to the medical office of the Investigator in order to view the SDand perform a comparison. This process is very tedious, time-consuming,and requires much traveling and cost.

Over the past two decades, the industry has adopted a new technology toenable a CRF to be presented to an Investigator in an electronic form.The electronic CRF (or eCRF) is typically a web-based form viewed via acomputer with areas of text representing questions followed by any oneof a variety of mechanisms to allow the Investigator to submit answers:open text fields, radio buttons, drop-down menus, etc. However, theprocess of filling out an online form representing an eCRF is stillperformed by the Investigator referencing the patient chart (SD).Therefore, this continues to be a transcription process and subject tohuman error. Therefore, even using eCRF, there is still a need for theSponsor to perform quality control checks through SDV.

There are advantages to using an eCRF, however, because there is nolonger a need for paper forms to be faxed between Investigator andSponsor, and electronic forms are more legible than handwritten forms.Also, eCRF’s can be programmed so that potential errors may be flaggedby the eCRF at the time of data entry. For example, if an Investigatorenters a heart rate value of 800, an eCRF can be programmed withcomputer code to detect when the entered value is out of range. Suchcomputer code is referred to as an Edit Check. In this example, an EditCheck could be used to alert the Investigator that the heart rate of 800is out of range. The Investigator would be able to immediately react tothe problematic data and make a correction. If a paper CRF were beingused, this same example would lead to many days lost in the datacleaning process for the clinical trial because the doctor might notnotice the error, the paper CRF would be faxed to the Sponsor, theerroneous data would be entered into a database, and many days to weekslater, an Edit Check would be programmed and applied at the databaselevel to flag the data as out-of-range.

These flags raised for problematic data are known as Queries. A reportof this Query would then have to be printed and faxed back to theInvestigator who would try to resolve the Query by referencing back tothe SD. This process of cleaning data is time consuming for any clinicaltrial, and generally adds weeks to months, and even years of time to thedrug development cycle. While the use of an eCRF can save some time inthe data cleaning process, significant time and expense is stillincurred in the process of programming Edit Checks. To sum, whether aSponsor uses a paper CRF or an eCRF, there are many weeks to monthsspent by data management personnel to program edit checks for eachquestion of a CRF. Also, the process of transcribing information from aSD to CRF (or eCRF) is still a point of potential human error, andtherefore still requires the Sponsor to perform SDV.

One prior art process for verifying clinical trial source data isdescribed in U.S. Pat. Application Publication US 2012/0096005 toO’Conner and partially described in FIG. 1 . Specifically, this priorart technique, inter alia, electronically acquires images of sourcedocuments, indexes the images and stores the images in a source databasein a predetermined order based on the indexing, selects an image fromthe source database, interfaces with a clinical database, andsimultaneously displays data from the clinical database alongside theselected image in a clinical research setting, as further describedtherein. However, this prior art technique still requires theInvestigator or a nurse to manually transcribe information from the SDto the eCRF, and does not provide reliable data accountability,Investigator verification of answers to the eCRF, or strong protectionsfor patient privacy.

In addition, pharmaceutical companies tend to keep their data transfersystems and informatics systems proprietary since they do not wantresearch data to go easily outside of their own corporate firewalls.Thus, computer systems and informatics systems of pharmaceuticalcompanies are not easily “plugged into” hospital systems. Thus, thereexists a need to safely and confidentially transmit and verify originalpatient data recorded in hospital systems and to provide a convenientand reliable way that complies with patient privacy restrictions toprovide necessary clinical trial data to informatics systems ofpharmaceutical companies which have engaged such hospital systems toparticipate in clinical trials for medical treatments developed by thecompanies.

SUMMARY OF THE INVENTION

The present invention provides an electronic data document (EDD) for usein a computerized clinical trial verification system. In an exemplaryembodiment, the EDD includes (1) first computer instructions associatedwith the EDD that permit a receiver of the EDD to validate a sender ofthe EDD and an electronic data structure of the EDD, (2) an image of asource document (SD) that comprises a record of at least one interactionbetween a clinical trial investigator and a patient enrolled in aclinical trial, (3) at least one revealed portion of the SD thatcomprises evidence relevant to at least one question in a clinical trialquestionnaire, and (4) at least one marking connecting the revealedportion to the at least one question.

In a further embodiment, the EDD further includes second computerinstructions associated with the EDD that mask all portions of the SDnot included in the revealed portion and that permit authorized personsto selectively unmask one or more portions of the SD that are notincluded in the revealed portion. In a further embodiment, the EDDfurther includes third computer instructions that permit one or moreauthorized persons to accept the revealed portion as sufficient evidenceto answer the at least one question.

In an exemplary embodiment, the EDD is encrypted. In a furtherembodiment, the EDD further includes fourth computer instructions thatpermit the investigator to associate an electronic signature with theEDD, thereby allowing the investigator to note that the EDD is truthfuland representative of the patient, dates, and information submitted inresponse to the clinical trial questionnaire. In a further embodiment,the EDD further includes fifth computer instructions that permit theinvestigator to associate an electronic signature with the revealedportion, thereby allowing the investigator to note that the revealedportion is truthful and representative of the patient and of datesassociated with the revealed portion. In a further preferred embodiment,the EDD is not saved as a file that can be recalled at a later time.

The present invention provides a computerized system and method forallowing at least one medical professional (Investigator) to answerquestions from a clinical trial questionnaire (case report form (CRF))pertinent to a clinical trial of a medical treatment. In an exemplaryembodiment, the system includes (1) a source document (SD) ingesterconfigured to allow the Investigator to answer the questions withdigital images of portions of the SD (SD revealed portions or snippets)as evidence for answers to the questions, where the SD includes adescription of at least one interaction between the Investigator and apatient enrolled in the clinical trial (Subject), (2) a SD snippetmarkup tool configured to allow the Investigator to annotate the SDsnippets, thereby allowing the Investigator to draw attention of theSponsor to information relevant to the clinical trial via annotated SDsnippets, (3) a sponsor viewing tool configured to allow a manufacturerof the medical treatment (Sponsor) to view the SD snippets and themarked SD snippets, and (4) a reviewing tool configured to allow theSponsor to accept the SD snippet images if the SD snippet images aresupportive or are representative of the answers to the questions and toreject the SD snippet images if the SD snippet images are not supportiveor are not representative of the answers to the questions.

In an exemplary embodiment, the sponsor viewing tool is configured to beresponsive to computer instructions that mask from viewing by theSponsor all portions of the SD that do not correspond to the SD snippetimages. In a further embodiment, the sponsor viewing tool is furtherconfigured to display to at least one authorized person at least oneportion of the SD that does not correspond to the SD snippet images. Ina further preferred embodiment, the sponsor viewing tool does not createany local or temporary copies of the SD or any portions thereof.

In a further embodiment, the SD ingester is further configured to allowthe Investigator to capture a digital image of the entire SD (SD fullimage). In a further embodiment, the SD ingester further associatescomputer instructions with the SD full range that mask the SD full imageand also are configured to display to at least one authorized person theSD full image. In a further preferred embodiment, the SD ingester doesnot create any local or temporary copies of the SD image.

In a further embodiment, the system further includes an electronicsignature tool configured to allow the Investigator to associate anelectronic signature with the SD snippet images, thereby allowing theInvestigator to note that the SD snippet images are truthful andrepresentative of the Subject, dates, and information submitted inresponse to the CRF. In a further embodiment, the SD ingester furtherincludes an electronic signature tool configured to allow theInvestigator to associate an electronic signature with the SD fullimage, thereby allowing the Investigator to note that the SD full imageis truthful and representative of the Subject, dates, and informationsubmitted in response to the CRF.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart of a prior art technique.

FIG. 2 is a diagram of a user interaction in accordance with anexemplary embodiment of the present invention.

FIG. 3 is a diagram of a user interaction in accordance with anexemplary embodiment of the present invention.

FIG. 4 is a diagram of a user interaction in accordance with anexemplary embodiment of the present invention.

FIG. 5 is a diagram of a computerized system in accordance with anexemplary embodiment of the present invention.

FIG. 6A is a flowchart in accordance with an exemplary embodiment of thepresent invention.

FIG. 6B is a flowchart in accordance with a further embodiment of thepresent invention.

FIG. 7 is a flowchart of the marking up step in accordance with anexemplary embodiment of the present invention.

FIG. 8A is a flowchart of the displaying step in accordance with anexemplary embodiment of the present invention.

FIG. 8B is a flowchart of the displaying step in accordance with afurther embodiment of the present invention.

FIG. 9A is a flowchart of the ingesting step in accordance with afurther embodiment of the present invention.

FIG. 9B is a flowchart of the ingesting step in accordance with afurther embodiment of the present invention.

FIG. 10 is a flowchart of the ingesting step in accordance with afurther embodiment of the present invention.

DESCRIPTION OF THE INVENTION

This invention provides a means of allowing Investigators to provideSponsors with SD image sections (snippets) corresponding to the answersto questions posed by the eCRF. Since the eCRF questions are beinganswered by images coming directly from the SD, it is no longer atranscription process, and therefore obviates the need to perform SDV.Also, since the SD is the ultimate resource of original data, there isvirtually no need for programming edit checks to evaluate the quality ofthe data or to do other time consuming data cleaning. The SD isconsidered to be a legal document and the information in it isconsidered to be final. Also, in modern times, most doctor’s offices andhospitals have adopted electronic medical records (EMR) and thesesystems already contain complex error-checking programming. Thisinvention enables Sponsors to leverage the error-checking that alreadyexists in EMR systems.

The current idea presents a process in which the Sponsor is able toperform single or double data entry directly from relevant portions ofthe SD, thus skipping the step where the Investigator fills out the CRFwith alphanumeric data. The invention involves a method in which theInvestigator fills out the CRF with images of select portions of the SDwhere the relevant alphanumeric information is visible. The SD imagescan be obtained by a digital camera for paper source documents or thescreen-capture capability within software for electronic SD. In order toprotect patient privacy as required by the Health Insurance Portabilityand Accountability Act (HIPAA), FDA Title 21 CFR Part 11, and other lawsand regulations, and to direct the Sponsor’s attention to only therelevant information, the Investigator is able to mark the images withdrawing and labeling tools. Also, to protect patient privacy, areas thatare not marked by the Investigator are made invisible to the Sponsor byelectronic masking such that the sponsor may see only the alphanumericinformation on the images that the Investigator decides are relevant andresponsive to the clinical trial.

Since the Investigator is no longer filling out a form, but rather,marking images taken from the original SD, there is no longer a risk fortranscription error. Since the Sponsor is viewing an exact digital imageof the section of the SD needed for the clinical study, single or doubledata entry is performed directly from an image of the SD, and thereforeeliminates or greatly reduces the need to perform in person SDverification.

The invention is a computer-implemented system and method for collectingclinical research data, utilized, inter alia, by a pharmaceuticalcompany or a medical device company for data entry and verification ofdata. Currently, pharmaceutical companies send representatives tomedical offices where the representative physically cross-checks thepharmaceutical company’s record with the medical records of the medicaloffice, entering study-relevant data from the medical records into thepharmaceutical company’s database and correcting erroneous entries. Thisprocess is inefficient and expensive. Proposed solutions for sharing thepatient record information online by giving the Sponsor direct access toall of the Investigator’s electronic medical records raise privacyconcerns - thus, the representative must physically go to the medicaloffice and will likely have to go through many paper and electronicdocuments to find the relevant information. The present invention offersa solution to sharing such information without requiring travel andwithout providing the pharmaceutical company unfettered access to apatient’s full medical record containing confidential patientinformation.

The present invention may be implemented by a physician or nurse takinga screen shot of a page (or snap shot of a particular section on apage), labeling that screen shot to identify the relevant data itcontains (e.g., temperature, blood pressure, etc.), and adding anycomments relating to the data or its application to a clinical study tothat screen shot. Thus, without having to enter patient information intoa new form, the doctor or nurse can identify information generallyrelevant to studies that might be performed by various pharmaceuticalcompanies. Similarly, a physician or nurse may take a photo (e.g., witha smart phone app) of paper test records unavailable on a computer,label that information with or without comment, and electronicallyinclude such test records using the same program. The patientinformation that is not selected/labeled by the physician iselectronically redacted, thus allowing only study-relevant material tobe shared electronically with the pharmaceutical company. The companyreceives this information in a manner such that only the portions of therecord that are labeled by the medical office are shown, eithersurrounded by redacted portions of the SD or alternatively showing justthe relevant data in each snap shot, one by one. This, in turn, showsthe pharmaceutical company all the data it needs to see and none of theinformation that is irrelevant to the study and/or raises privacyissues. Because the sections of a medical record are selected andlabeled by the medical office, the pharmaceutical company can determinewhat information it wants to see on a study-by-study basis using aClinical Research Form and the present invention will provide thatinformation. This will save the pharmaceutical company time in having toreview an entire medical file to verify the information. And theinformation can be shared electronically without raising privacyconcerns because only study-relevant information can be viewed by theSponsor’s reviewers.

Furthermore, if redacted portions of the medical file need to bereviewed for regulatory or fraud elimination purposes (e.g., by an FDAauditor, or a high-level executive of the Sponsor company), a user withthe proper authorization is able to view the redacted information in alimited but sufficient manner (e.g., a viewport). Thus, the inventionmasks the confidential information from general view but retains thedata of that information as part of the redacted SD in case anauthorized person needs to view it to, e.g., confirm that the data beingshared is in fact related to a particular patient.

Referring to FIG. 2 , in an exemplary embodiment, the present inventionallows a physician (Investigator) or nurse to select particular data 220and label it from a complete medical record 210. The present inventionallows the Investigator to use additional labels 230 as well. TheInvestigator may select particular portions 220 (i.e., captures) of themedical record via the invention, including any scanned paper charts,and add them as chart images 240. The patient’s prior interactionshistory 250 is also available for use by the Investigator to select toadd as a chart image.

Referring to FIG. 3 , in an exemplary embodiment, the present inventionallows a pharmaceutical company (Sponsor) to view a redacted page 310 ofthe SD medical record 210, where only the information relevant to thestudy 220 is shown with the rest of the document redacted. Referring toFIG. 4 , in an exemplary embodiment, the present invention allows anauthorized user to view otherwise redacted information 410 via a“viewport” tool.

Electronic Data Document

In an exemplary embodiment, the present invention provides an electronicdata document (EDD) for use in a computerized clinical trialverification system. In an exemplary embodiment, the EDD includes (1)first computer instructions associated with the EDD that permit areceiver of the EDD to validate a sender of the EDD and an electronicdata structure of the EDD, (2) an image of a source document (SD) thatcomprises a record of at least one interaction between a clinical trialinvestigator and a patient enrolled in a clinical trial, (3) at leastone revealed portion of the SD that comprises evidence relevant to atleast one question in a clinical trial questionnaire, and (4) at leastone marking connecting the revealed portion to the at least onequestion.

In a further embodiment, the EDD further includes second computerinstructions associated with the EDD that mask all portions of the SDnot included in the revealed portion and that permit authorized personsto selectively unmask one or more portions of the SD that are notincluded in the revealed portion. In a further embodiment, the EDDfurther includes third computer instructions that permit one or moreauthorized persons to accept the revealed portion as sufficient evidenceto answer the at least one question.

In a further embodiment, the EDD further includes at least one questionfrom the clinical trial questionnaire. For example, one of the questionsfrom the questionnaire could be part of the EDD (e.g., what is thepatient’s blood pressure?). In such an example, the “answer” to thatquestion would be the revealed portion of the SD that includes evidencerelevant to at least one question in the clinical trial questionnaire(which shows the entry for the blood pressure). Also, in such anexample, the marking that is dragged on and associated with the revealedportion (e.g., “Blood pressure”) would link the question to the revealedportion (the “evidence”). In an exemplary embodiment, the EDD includesquestions that are automatically superimposed on the SD, such that theinvestigator could reveal relevant portions of the SD to answer thequestions.

In an exemplary embodiment, the EDD is encrypted. In a furtherembodiment, the EDD further includes fourth computer instructions thatpermit the investigator to associate an electronic signature with theEDD, thereby allowing the investigator to note that the EDD is truthfuland representative of the patient, dates, and information submitted inresponse to the clinical trial questionnaire. In a further embodiment,the EDD further includes fifth computer instructions that permit theinvestigator to associate an electronic signature with the revealedportion, thereby allowing the investigator to note that the revealedportion is truthful and representative of the patient and of datesassociated with the revealed portion.

Computerized System

Referring to FIG. 5 , in an exemplary embodiment, the present inventionprovides a computerized system for allowing at least one medicalprofessional (Investigator) to answer questions from a clinical trialquestionnaire (case report form (CRF)) pertinent to a clinical trial ofa medical treatment. In an exemplary embodiment, the system includes asource document (SD) ingester 510 configured to allow the Investigatorto answer the questions with digital photographs of portions of the SD(SD snippets) as evidence for answers to the questions, where the SDincludes a description of at least one interaction between theInvestigator and a patient enrolled in the clinical trial (Subject), aSD snippet markup tool 520 configured to allow the Investigator toannotate SD snippets 220, thereby allowing the Investigator to drawattention of the Sponsor to information relevant to the clinical trialvia annotated SD snippets, a sponsor viewing tool 530 configured toallow a manufacturer of the medical treatment (Sponsor) to view the SDsnippets and the annotated SD snippets (SD snippet images), and areviewing tool 540 configured to allow the Sponsor to accept the SDsnippet images if the SD snippet images are supportive and arerepresentative of the answers to the questions and to reject the SDsnippet images if the SD snippet images are not supportive and are notrepresentative of the answers to the questions. In an exemplaryembodiment, the description includes alphanumeric characters written ortyped by the Investigator.

In an exemplary embodiment, each of the snippets 220 are digitalphotographs or an output of an imaging device, where the imaging devicemay be a digital camera, computer screen capture software, a mobiletelephone, a medical scanner or imaging machine and a portable computer.For example, if medical records are in paper form, an Investigator maytake photographs of relevant medical charts of the Subject with a mobiletelephone. In another exemplary embodiment, the description includes achart or other representation of patient-related data obtained fromtesting the patient.

In an exemplary embodiment, SD snippet markup tool 520 includes computersoftware, where the computer software is selected from the groupconsisting of a computer software drawing tool, a computer softwarelabeling tool, mobile telephone application software configured toreceive stylus input, and mobile telephone application softwareconfigured to receive touch screen input. For example, if medicalrecords are in paper form and the Investigator has obtained SD snippetswith a mobile telephone, the Investigator may mark key areas of the SDsnippets via a stylus or a finger on the screen of the mobile telephone.In an exemplary embodiment, sponsor viewing tool 530 is configured tomask from viewing by the Sponsor all portions of the SD that do notcorrespond to the SD snippet images. In a further embodiment, sponsorviewing tool 530 is further configured to display to at least oneauthorized person at least one portion of the SD that does notcorrespond to the SD snippet images.

In a further embodiment, SD ingester 510 is further configured to allowthe Investigator to capture a digital image of the entire SD (SD fullimage). In a further embodiment, SD ingester 510 further includes a SDfull image viewing tool configured to display to at least one authorizedperson the SD full image. For example, authorized personnel may includefederal regulators (e.g., FDA personnel), privileged quality assuranceadministrators of the clinical trial, or study monitors.

In a further embodiment, the system further includes an electronicsignature tool configured to allow the Investigator to associate anelectronic signature with the SD snippet images, thereby allowing theInvestigator to note that the SD snippet images are truthful andrepresentative of the Subject, dates, and information submitted inresponse to the CRF. In a further embodiment, SD ingester 510 furtherincludes an electronic signature tool configured to allow theInvestigator to associate an electronic signature with the SD fullimage, thereby allowing the Investigator to note that the SD full imageis truthful and representative of the Subject, dates, and informationsubmitted in response to the CRF. In an exemplary embodiment, theelectronic signature includes a two token code that is kept secret bythe Investigator.

Method

Referring to FIG. 6A, in an exemplary embodiment, the present inventionprovides a method for allowing at least one medical professional(Investigator) to answer questions from a clinical trial questionnaire(case report form (CRF)) pertinent to a clinical trial of a medicaltreatment. In an exemplary embodiment, the method includes a step 610 ofingesting a source document (SD), thereby allowing the Investigator toanswer the questions with digital images of portions of the SD (SDsnippets) as evidence for answers to the questions, wherein the SDcomprises a description of at least one interaction between theInvestigator and a patient enrolled in the clinical trial (Subject), astep 620 of marking up the SD snippets, thereby allowing theInvestigator to mark the SD snippets 220, thereby allowing theInvestigator to draw attention of the Sponsor to information relevant tothe clinical trial via marked SD snippets, a step 630 of displaying SDsnippets 220 and the marked SD snippets (SD snippet images) to amanufacturer of the medical treatment (Sponsor), and a step 640 ofreviewing the SD snippet images, thereby allowing the Sponsor to acceptthe SD snippet images if the SD snippet images are supportive and arerepresentative of the answers to the questions and to reject the SDsnippet images if the SD snippet images are not supportive and are notrepresentative of the answers to the questions.

In an exemplary embodiment, each of the digital images 220 includes anoutput of an imaging device, where the imaging device is selected fromthe group consisting of a digital camera, computer screen capturesoftware, a mobile telephone, a medical imaging device such as an X-ray,NMR, or CT scanner, and a portable computer. For example, if medicalrecords are in paper form, an Investigator may take photographs ofrelevant medical charts of the Subject with a mobile telephone.

Referring to FIG. 7 , in an exemplary embodiment, marking up step 620includes a step 710 of executing computer software, where the computersoftware is selected from the group consisting of a computer softwaredrawing tool, a computer software labeling tool, a mobile telephoneapplication software configured to receive stylus input, and a mobiletelephone application software configured to receive touch screen input.Referring to FIG. 8A, in an exemplary embodiment, displaying step 630includes a step 810 of masking from viewing by the Sponsor all portionsof the SD that do not correspond to the SD snippet images. Referring toFIG. 8B, in a further embodiment, displaying step 630 further includes astep 820 of displaying to at least one authorized person at least oneportion of the SD that does not correspond to the SD snippet images.

Referring to FIG. 9A, in a further embodiment, ingesting step 610further includes a step 910 of capturing a digital image of the entireSD (SD full image). Referring to FIG. 9B, in a further embodiment,ingesting step 610 further includes a step 920 of displaying the SD fullimage or necessary parts thereof to at least one authorized person. Forexample, authorized personnel may include federal regulators (e.g., FDApersonnel), privileged quality assurance administrators of the clinicaltrial, or study monitors.

Referring to FIG. 6B, in a further embodiment, the method furtherincludes a step 650 of allowing the Investigator to associate anelectronic signature with the SD snippet images, thereby allowing theInvestigator to note that the SD snippet images are truthful andrepresentative of a particular Subject, dates, and information submittedin response to the CRF. Referring to FIG. 10 , in a further embodiment,ingesting step 610 further includes a step 1010 of allowing theInvestigator to associate an electronic signature with the SD fullimage, thereby allowing the Investigator to note that the SD full imageis truthful and representative of the Subject, dates, and informationsubmitted in response to the CRF.

General

The present invention can take the form of an entirely hardwareembodiment, an entirely software embodiment, or an embodiment containingboth hardware and software elements. In an exemplary embodiment, thepresent invention is implemented in software, which includes but is notlimited to firmware, resident software, and microcode. Any conventionalEMR system can be used as a source of SD, such as Cerner, Epic Systemsand Allscripts. Preferably, the systems and methods of the presentinvention are implemented in a client/server network connected via theInternet.

The systems and methods of the present invention will also preferablyuse data security, encryption, and data capture and transfer protocolsthat will enhance patient privacy and security and add desirableauthentication and verification features. Preferably, all data will betransferred over SSL connections (also known as HTTPS). Preferably, thesystems and methods of the invention will use data encryption(public/private key pair) to protect patient medical records representedin SD media, and data encryption will protect both data and media whilethey are stored and while they are being transferred, ensuring that onlythe intended recipients are able to access/view them. Preferably, everyuser must be authenticated on the system by logging in with theirprivate credentials. Preferably, during each interaction with theserver, the server confirms the authenticity of the request forinteraction by authentication tokens issued by the server. Preferably,the system will require the users to change their passwordsperiodically. Preferably, users will only have access to thefunctionality assigned to them by the system administrator. Preferably,information such as patient or subject ID, data capture date, and othernecessary identifying information is embedded in the SD image itself aswell as included in metadata, and accessible to qualified users andviewers of the SDD

In another preferred embodiment, no media or data is saved to any localmachine or device, either by the machine or device as it is created orby the Sponsor or Investigator when viewing it. Rather, data is captureddirectly from the screen output by the inventive software and is nothandled by the native Operating System, which might write that data todisk, even if only as temporarily cached files. Any additional imageprocessing that may be required, such as file compression for storage,is handled by servers away from the local machine or device. Preferably,the computer systems and programs used in embodiments of the inventiondo not save the SDD or other files created incident to the operation ofthe invention as a file that can be recalled at a later time. Screenshotcaptures can be obtained from any EMR software running on the samemachine as the inventive software, such that the EMR software displaysits information on the same screen(s) as are accessible by softwareimplementing the invention. Additional digital media imported by theinvention from any external source, such as photographs of paperdocuments or medical scans, are treated in the same manner as screenshotcaptures once loaded.

Furthermore, the present invention can take the form of a computerprogram product or products accessible from a computer-usable orcomputer-readable medium providing program code for use by or inconnection with a computer system or any instruction execution system.The computer program product includes the instructions that implementthe method of the present invention. A computer-usable or computerreadable medium can be any apparatus that can contain, store,communicate, propagate, or transport the program for use by or inconnection with the instruction execution system, apparatus, or device.The medium can be an electronic, magnetic, optical, electromagnetic,infrared, or semiconductor system (or apparatus or device) or apropagation medium. Examples of a computer-readable medium include asemiconductor or solid-state memory, magnetic tape, a removable computerdiskette, a random access memory (RAM), a read-only memory (ROM), arigid magnetic disk, and an optical disk. Current examples of opticaldisks include compact disk-read only memory (CD-ROM), compactdisk-read/write (CD-R/W), and DVD.

A computer system suitable for storing and/or executing program codeincludes at least one processor coupled directly or indirectly to memoryelements through a system bus. The memory elements include local memoryemployed during actual execution of the program code, bulk storage, andcache memories that provide temporary storage of at least some programcode to reduce the number of times code is retrieved from bulk storageduring execution. Input/output (I/O) devices (including but not limitedto keyboards, displays, pointing devices, etc.) can be coupled to thecomputer system either directly or through intervening I/O controllers.Network adapters may also be coupled to the computer system in order toenable the computer system to become coupled to other computer systemsor remote printers or storage devices through intervening private orpublic networks. Modems, cable modems, and Ethernet cards are just a fewof the currently available types of network adapters. The computersystem can also include an operating system and a computer file-system.

It is to be understood that the above description and examples areintended to be illustrative and not restrictive. Many embodiments willbe apparent to those of skill in the art upon reading the abovedescription and examples. The scope of the invention should, therefore,be determined not with reference to the above description and examples,but should instead be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. The disclosures of all articles and references, includingpatent applications and publications, are incorporated herein byreference for all purposes.

What is claimed is:
 1. A computerized system for answering at least onequestion in an electronic Case Report Form (eCRF) in a clinical trialstudy, the system comprising: at least one processor running an EMRsystem on a first device, wherein the EMR system includes at least onepatient source document displayed on a display associated with the firstdevice, the source document comprising a record of at least one datavalue associated with a patient enrolled in a clinical trial; the atleast one processor providing a source document (SD) ingester, the SDdocument ingester configured to create a source document (SD) snippet,wherein the SD snippet consists of text automatically recognized andoutput by computer screen capture software installed on the firstdevice; and the at least one processor having a SD snippet markup tool,the SD snippet markup tool configured to allow the SD snippet to beselected as relevant to the answer of at least a portion of the at leastone question in the eCRF.
 2. The computerized system as recited in claim1, wherein at least one question is superimposed on the first devicedisplay screen.
 3. The computerized system as recited in claim 1,wherein the SD snippet is not saved to the first device.
 4. Thecomputerized system as recited in claim 1, wherein the SD snippet ishandled independently of the first device native operating system. 5.The computerized system as recited in claim 1, further comprising the atleast one processor including an electronic signature tool configured toallow an electronic signature with the SD snippet, wherein theelectronic signature confirms the SD snippet is representative ofinformation from the source document.
 6. A method for answering at leastone question in an electronic Case Report Form (eCRF) in a clinicaltrial study, the method comprising: running an EMR system on a firstdevice, wherein the EMR system includes at least one patient sourcedocument displayed on a display associated with the first device, thesource document comprising a record of at least one data valueassociated with a patient enrolled in a clinical trial; ingesting asource document with a source document (SD) ingester; creating a sourcedocument (SD) snippet, wherein the SD snippet consists of textautomatically recognized and output by computer screen capture softwareinstalled on the first device; and marking the SD snippet using a SDsnippet markup tool, wherein the SD snippet markup tool is configured toallow the SD snippet to be selected as relevant to the answer of atleast a portion of the at least one question in the eCRF.
 7. The methodas recited in claim 6, further comprising superimposing the at least onequestion on the display associated with the first device.
 8. The methodas recited in claim 6, wherein the SD snippet is not saved to the firstdevice.
 9. The method as recited in claim 6, wherein the SD snippet ishandled independently of the first device native operating system. 10.The method as recited in claim 6, further comprising signing the SDsnippet using an electronic signature tool, wherein the electronicsignature tool is configured to associate an electronic signature withthe SD snippet, wherein the electronic signature provides confirmationthat the SD snippet is representative of information from the sourcedocument.
 11. An electronic data document (EDD) in a non-transitorycomputer-readable medium for use in a computerized clinical trialverification system, the system comprising: a first computer programthat can be used to create the EDD and running an EMR system on a firstdevice, wherein the EMR system includes at least one patient sourcedocument displayed on a display associated with the first device, thesource document comprising a record of at least one data valueassociated with a patient enrolled in a clinical trial; and a secondcomputer program that can read and modify the EDD, the EDD comprising:integrated computer instructions that are compatible with the firstcomputer program and the second computer program and integrated with theEDD; ingesting a source document with a SD ingester, wherein theintegrated computer instructions further comprise: first computerinstructions that permit creating a source document (SD) snippet,wherein the SD snippet consists of text automatically recognized andoutput by computer screen capture software installed on the firstdevice; and second computer instruction that permit marking the SDsnippet using a SD snippet markup tool, wherein the SD snippet markuptool is configured to allow the SD snippet to be selected as relevant tothe answer of at least a portion of the at least one question in anelectronic case report form (eCRF) in the computerized clinical trialverification system.
 12. The EDD as recited in claim 11, wherein thecomputer instructions further comprise third computer instructions thatpermit superimposing the at least one question on the display associatedwith the first device.
 13. The EDD as recited in claim 11, wherein theSD snippet is not saved to the first device.
 14. The EDD as recited inclaim 11, wherein the SD snippet is handled independently of the firstdevice’s native operating system.
 15. The EDD as recited in claim 11,wherein the computer instructions further comprise fourth computerinstructions that permit signing the SD snippet using an electronicsignature tool, wherein the electronic signature tool is configured toassociate an electronic signature with the SD snippet, wherein theelectronic signature provides confirmation that the SD snippet isrepresentative of information from the source document.